The effect of estradiol on testicular testosterone biosynthesis

Natwar R. Kalla, Bruce C. Nisula, Raymond Menard, D. Lynn Loriaux

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Abstract

The presence of an estrogen receptor in Leydig cell cytosol suggests that estrogen could have a direct action on Leydig cell function. We have studied the direct effects of estradiol (E2) on Leydig cell testosterone (T) biosynthesis using hypophysectomized rats treated daily for 4 days with 400 IU hCG (Pregnyl) and 1 IU human FSH (Pergonal), a model that eliminates the possibility of feedback effects of E2 on gonadotropin secretion. E2 was administered in sc silastic capsules. Rats having capsules that contained E2 were compared to rats having capsules that were empty. E2 treatment increased plasma E2 concentration from 380 ± 56 to 670 ± 64 pg/ml (mean ± SE; < 0.01) and decreased plasma T levels from 999 ± 167 to 461 ± 156 ng/100 ml (< 0.01). These plasma steroid changes were associated with a decrease in testis weight from 1167 ± 170 to 870 ± 72 mg (< 0.01). No change was seen in prostate or seminal vesicle weight. Three possible mechanisms by which E2 treatment could decrease plasma T were investigated, viz. changes in clearance of plasma T, changes in testicular hCG binding, and altered Leydig cell T biosynthesis. Plasma T clearance was not significantly changed by E2 treatment. hCG binding by testis homogenates was decreased from 4.70 ± 0.63 to 3.12 ± 0.26 ng hCG/testis (< 0.05), in E2-treated animals. E2 treatment decreased testicular T content from 347 ± 70 to 226 ± 15 ng/testis (< 0.05). Testicular androstenedione and dehydroepiandrosterone were also decreased. Testicular progesterone content increased from 13.7 ± 2.9 to 80.2 ± 10.7 ng/testis (< 0.01), and testicular 17-hydroxyprogesterone increased from 14.6 ± 3.2 to 53.4 ± 5.7 ng/testis (< 0.01). The pregnenolone content of the testis was not changed by estrogen therapy (13.78 ± 5.8 vs. 21.26 ± 10.5 ng/testis). These changes in testicular steroid content were associated with a decrease in microsomal cytochrome P-450 (1.38 ± 0.08 to 0.71 ± 0.13 nmol/testis; < 0.01), 17α-hydroxylase activity (1.197 ± 0.386 to 0.157 ± 0.029 nmol/testis-min; < 0.05), and 17β-dehydrogenase (0.990 ± 0.171 to 0.443 ± 0.164 nmol/testis · min; < 0.02). These findings indicate that E2 in vivo can directly interfere with Leydig cell function. The principal manifestation of the inhibitory effect of E2 on T biosynthesis is an apparent reduction in 17–20 desmolase activity.

Original languageEnglish (US)
Pages (from-to)35-39
Number of pages5
JournalEndocrinology
Volume106
Issue number1
DOIs
StatePublished - Jan 1980

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ASJC Scopus subject areas

  • Endocrinology

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